Antibiotics used in low doses during early life alter the murine colonic microbiome and adiposity. This study investigated the effects of subtherapeutic antibiotic treatment on the gut microbiome and metabolic outcomes in young mice. The research found that exposure to antibiotics increased adiposity and metabolic hormones in mice, with significant changes in the composition and function of the gut microbiome. The microbiome showed shifts in taxonomic groups, increased short-chain fatty acid (SCFA) levels, and altered regulation of lipid and cholesterol metabolism. These changes were observed in multiple antibiotic groups, indicating that the effects are not specific to a single antibiotic class. The study also found that early-life exposure to antibiotics increased bone mineral density and levels of gastric inhibitory polypeptide (GIP), a hormone involved in energy homeostasis. Despite no significant changes in overall microbial counts, the composition of the gut microbiome was altered, with increased representation of certain bacterial taxa, such as Lachnospiraceae. These changes were associated with increased SCFA production, which may contribute to the observed increase in adiposity. The study further demonstrated that antibiotic exposure altered the regulation of hepatic lipid and cholesterol metabolism, with changes in gene expression related to fatty acid metabolism and lipid synthesis. These findings suggest that early-life antibiotic exposure can have long-term effects on metabolic health, potentially influencing adiposity and bone development. The research highlights the importance of the gut microbiome in metabolic regulation and suggests that early-life antibiotic exposure may have significant consequences for host metabolism. The study provides evidence that the microbiome can be manipulated by antibiotics, leading to changes in metabolic pathways and potentially affecting long-term health outcomes. The findings underscore the need for further research into the effects of antibiotic use on the microbiome and its implications for human health.Antibiotics used in low doses during early life alter the murine colonic microbiome and adiposity. This study investigated the effects of subtherapeutic antibiotic treatment on the gut microbiome and metabolic outcomes in young mice. The research found that exposure to antibiotics increased adiposity and metabolic hormones in mice, with significant changes in the composition and function of the gut microbiome. The microbiome showed shifts in taxonomic groups, increased short-chain fatty acid (SCFA) levels, and altered regulation of lipid and cholesterol metabolism. These changes were observed in multiple antibiotic groups, indicating that the effects are not specific to a single antibiotic class. The study also found that early-life exposure to antibiotics increased bone mineral density and levels of gastric inhibitory polypeptide (GIP), a hormone involved in energy homeostasis. Despite no significant changes in overall microbial counts, the composition of the gut microbiome was altered, with increased representation of certain bacterial taxa, such as Lachnospiraceae. These changes were associated with increased SCFA production, which may contribute to the observed increase in adiposity. The study further demonstrated that antibiotic exposure altered the regulation of hepatic lipid and cholesterol metabolism, with changes in gene expression related to fatty acid metabolism and lipid synthesis. These findings suggest that early-life antibiotic exposure can have long-term effects on metabolic health, potentially influencing adiposity and bone development. The research highlights the importance of the gut microbiome in metabolic regulation and suggests that early-life antibiotic exposure may have significant consequences for host metabolism. The study provides evidence that the microbiome can be manipulated by antibiotics, leading to changes in metabolic pathways and potentially affecting long-term health outcomes. The findings underscore the need for further research into the effects of antibiotic use on the microbiome and its implications for human health.